Adiponutrin, a Transmembrane Protein Corresponding to a Novel Dietary- and Obesity-linked mRNA Specifically Expressed in the Adipose Lineage

Abstract

We have used a mRNA differential display technique to identify new genes involved in the reprogramming of gene expression during the adipose conversion of mouse 3T3 preadipocyte cell lines. We report here on the identification and cloning of a novel adipose-specific cDNA encoding a predicted membrane protein of 413 amino acids. The level of the corresponding 3.2-kilobase mRNA is tremendously increased during 3T3-L1 and 3T3-F442A differentiation into adipocytes. A single, very abundant 3.2-kilobase transcript is also found in inguinal and epididymal white adipose tissues and in interscapular brown adipose tissue but not in any other tissues examined. Its expression in adipose tissue is under tight nutritional regulation. The level of this novel 3.2-kilobase transcript becomes virtually nondetectable during fasting but is dramatically increased when fasted mice are refed a high carbohydrate diet. Based on its adipose specificity and dietary regulation, the novel gene product has been designated adiponutrin. The expression of adiponutrin mRNA is also 50-fold elevated in genetically obese fa/fa rats, indicating a link between adiponutrin and obesity. Western blot and confocal imagery analyses with epitope-tagged protein transiently expressed in 3T3-L1 adipocytes, and COS cells show that adiponutrin strictly localizes to membranes and is absent from the cytosol. Sequence analysis reveals homologies with several other members of related eukaryotic proteins, including a human paralog, which has been recently described in vesicular transport mechanisms. This leads us to suggest that adiponutrin could be involved in vesicular targeting and protein transport restricted to the adipocyte function.

Variant in PNPLA3 is associated with alcoholic liver disease

“…The gene is highly expressed in adipocytes and liver 7 , and the protein may have a role in energy homeostasis 13 . Obesity and diabetes are known risk factors for non alcoholic as well as alcoholic liver disease, and expression of PNPLA3 is correlated with obesity 6 .…”

Diet-induced obesity affects expression of adiponutrin/PNPLA3 and adipose triglyceride lipase, two members of the same family

“…1 They are under tight nutritional regulation having an opposite pattern in response to feeding conditions and, apparently, and opposite role in energy metabolism. [2][3][4][5][6][7] Adiponutrin, also known as PNPLA3, is a non-secreted transmembrane protein. Its expression sharply decreases in adipose tissue after fasting and is strongly upregulated by feeding [2][3][4][5] through the mediation of insulin and glucose release.…”

Les protéines à domaine patatine

“…Adiponutrine L'adiponutrine (PNPLA3) est le premier gène de ce groupe à avoir été caractérisé [31]. Chez la souris, l'expression du gène est presque exclusivement restreinte à l'adipocyte alors que chez l'homme, on la détecte aussi dans le foie et les muscles squelettiques [28].…”

“…Les conditions nutritionnelles dans le tissu adipeux contrôlent l'expression de l'adiponutrine qui est induite au cours de la différenciation adipocytaire. Indétectable à jeun, elle est très fortement augmentée après une prise alimentaire [31]. L'insuline et le glucose induisent l'expression de l'adiponutrine [32] qui est surexprimée dans des modèles murins d'obésité [31] ainsi que chez des patients obèses ou insulinorésistants [32].…”

“…L'insuline et le glucose induisent l'expression de l'adiponutrine [32] qui est surexprimée dans des modèles murins d'obésité [31] ainsi que chez des patients obèses ou insulinorésistants [32]. La protéine est localisée au niveau des structures membranaires du cytoplasme comme l'appareil de Golgi ou le réticulum endoplasmique, site principal de synthèse des lipides dans les cellules de mammifères [31]. .…”